基于网络药理学和分子对接技术分析柴胡-白芍药对治疗肝损伤的作用机制

Exploring the Mechanism of Radix Bupleuri—Paeoniae Radix Alba Drug Pair Treating Liver Injury based on Network Pharmacology and Molecular Docking

目的基于网络药理学和分子对接技术探讨柴胡-白芍药对治疗肝损伤(LI)的作用机制。方法运用中药系统药理学数据库与分析平台(TCMSP)以口服生物利用度(OB)≥0.30且类药性(DL)≥0.18为条件筛选得到柴胡-白芍药对的活性成分化合物及对应靶点,运用Pubchem平台获取靶点Canonical SMILES号,通过SwissTargetPrediction及TargetNet数据库预测并获取有效靶点;运用GeneCards及OMIM数据库获取LI疾病基因靶点;Venn2.1平台进行拓扑分析,获取疾病与活性成分的交集靶点;将交集靶点导入String数据库,获取蛋白质-蛋白质相互作用(PPI)网络,靶点网络以PPI阈值0.9为标准,隐藏游离靶点,下载PPI可视化图和交集靶点.TSV文件;运用Excel建立“药物-活性成分-靶点”表,导入Cytoscape 3.9软件构建关系网络,并进行可视化;运用DAVID数据库将柴胡-白芍药对治疗LI的作用靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)富集分析,获取数据,并利用微生信数据可视化平台进行可视化。根据Degree值运用Auto Dock Vina v.1.2.0软件将排名前5的核心作用靶点与柴胡-白芍的核心活性成分进行分子对接,得到对接结合能以及对接结果文件。结果共筛选得到柴胡-白芍药对活性成分27个,包括山柰酚、异鼠李素、槲皮素、β-谷甾醇等;柴胡-白芍药对抗LI的核心靶点216个,排名前5的靶点分别为蛋白激酶B1(AKT1)、肿瘤坏死因子(TNF)、白白细胞介素6(IL6)、血管内皮生长因子A(VEGFA)、表皮生长因子受体(EGFR);KEGG富集分析结果显示,柴胡-白芍药对抗LI主要涉及PI3K/AKT信号通路、MAPK信号通路等。分子对接结果显示,活性成分与核心靶点的结合构象稳定。结论柴胡-白芍药对可能通过作用于AKT1、TNF、IL6、VEGFA、EGFR等核心靶点,调控PI3K/AKT信号通路、MAPK信号通路等相关通路,发挥治疗LI的作用。

Objective To explore the mechanism of Radix Bupleuri—Paeoniae Radix Alba drug pair in treating liver injury(LI)based on network pharmacology and molecular docking techniques.Methods Using TCMSP database with OB≥0.30,DL≥0.18 was used to select the active compound of the Radix Bupleuri—Paeoniae Radix Alba drug pair and the corresponding target.Using the Pubchem platform to obtain the target Canonical SMILES number,Predict and obtain effective targets through SwissTargetPrediction and Targetnet databases.Using GeneCards and OMIM databases to obtain gene targets for liver injury diseases.Veen 2.1 platform for topological analysis,to obtain the intersection targets of disease and active components.Import of the intersection targets into the STRING database and get the PPI network.The target network using a PPI threshold of 0.9 hide the free targets.The PPI visualization maps and the intersection targets were downloaded.TSV file.Use Excel to establish"medicine-active ingredient-target"table,import Cytoscape 3.9 software to build relationship network,and visualize.Use DAVID database to make Radix Bupleuri—Paeoniae Radix Alba drug pair targets against liver damage for GO function and KEGG enrichment analysis,obtain the data and use micro-letter data visualization platform.According to the Degree value,the top 5 core targets and the core active components of Radix Bupleuri—Paeoniae Radix Alba drug pair were connected by Auto Dock Vina v.1.2.0 software,and the protein binding energy heat map and visualization map were obtained.Results 27 active ingredients were obtained by network pharmacological analysis,including kaempferol,isorhamnetin,quercetin andβ-sitosterol.216 core targets of Radix Bupleuri—Paeoniae Radix Alba drug pair against liver injury,and the top 5 targets were AKT1,TNF,IL6,VEGFA and EGFR.KEGG enrichment analysis showed that Radix Bupleuri—Paeoniae Radix Alba drug pair against liver injury mainly involved PI3K/AKT signaling pathway,MAPK signaling pathway,etc.Molecular docking results showed that the binding energy conformation of the active component with the core target.Conclusion Radix Bupleuri—Paeoniae Radix Alba drug pair may play a role in fighting liver injury by acting on AKT1,TNF,IL6,VEGFA,EGFR,regulating PI3K/AKT signaling signaling pathway,MAPK signaling pathway.